Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs and vehicles for HIV dissemination in the infected human host. Understanding HIV dynamics in resident MP is important since viral sequestration in tissue occurs as a consequence of disease progression.
One body tissue in which restricted infection of MP and virus compartmentalization can occur is the placenta. Trophoblasts are susceptible to infection but show restricted viral replication, whereas productive viral infection occurs in placental macrophages (PM). Interestingly, the levels of HIV replication in PM are at least 10-fold lower than what is seen in peripheral blood monocyte-derived macrophages (MDM. Decreased CCR5 expression has been associated with restricted HIV replication in PM, but the intracellular mechanisms that affect it are not known.
Previously, several host factors were identified to be associated with HIV restriction in the placenta. Leukemia inhibitory factor (LIF) is a placenta-secreted protein that limits viral replication in the placenta. The pregnancy-related hormone human chorionic gonadotropin beta-subunit (b-hCG) is produced by trophoblasts and upon addition to placenta explants inhibits HIV expression and progeny virion production. hCG inhibited HIV RT and p24 antigen from HIV-infected lymphocytes when they were co-cultured with placental trophoblasts. A dose-dependent inhibition of HIV infection in hCG-treated tissue explants was found. Correlations were made between hCG concentrations in blood and viral load or HIV infection. However, it was unknown which host factors account for PM infection and viral growth.